(In)organic anions as carbonic anhydrase inhibitors

Carbonic anhydrases (CAs, EC 4.2.1.1) are widespread enzymes in all life kingdoms with five distinct genetic families known to date, the α-, β-, γ-, δ- and ζ-CAs. With the exception of the δ-class, which is less investigated to date, enzymes from the remaining classes found in vertebrates, corals, fungi, bacteria and archaea have been studied for their inhibition with simple inorganic anions as well as more complex inorganic and organic ones. In this paper we review the available data for the inhibition of these enzymes with all anions except sulfonamides and their bioisosteres (sulfamates, sulfamides) which have been reviewed earlier. Anion inhibitors are important both for understanding the inhibition/catalytic mechanisms of these enzymes and for designing novel types of inhibitors which may have clinical applications for the management of a variety of disorders in which CAs are involved. Environmental aspects of CO2 fixation by CAs present in plants, corals, algae or diatoms and how this may be affected by inhibitors are also discussed.

Graphical abstractThe active site of the Cd-R1 ξ-Carbonic Anhydrase (CA) from Thalassiossira weissflogii complexed with acetate. Cd(II) is coordinated by one His and two Cys ligands (as the Zn(II) in β-CAs), by an acetate ion and a water molecule, in a trigonal bipyramidal geometry of the metal ion.Figure optionsDownload full-size imageDownload as PowerPoint slide